The nature of the immune response in the intestine is one of suppression or controlled inflammation. Several groups have suggested that this type of response is dictated by the nature of the microenvironment in which the mucosa-associated lymphoid tissue resides. Several factors come into play to promote this suppressed state: regulatory T cells, poorly reactive macrophages, unusual T lymphocyte populations (intraepithelial and lamina propria lymphocytes) and unique antigen presenting cells. Included in this later population are intestinal epithelial cells. Evidence has been provided for such functional properties in both rat, mouse and man. In rat and man, antigens presented by these cells result in the selective activation of CD8+ suppressor T cells.
Two cell surface molecules involved in this interaction have been identified: the nonclassical class I molecule CD1d and a surface glycoprotein recognized by two anti-epithelial cell monoclonal antibodies (mAbs), B9 and L12, called gp180. These two mAbs block the selective proliferation of CD8+ T cells and inhibit the phosphorylation of the CD8 associated kinase p56 l ck in IEC: T cell co-cultures. Purified gp180 (mAb B9 affinity purified material) binds to CD8, activates p56 l ck and forms a complex with CD1d.
It is towards the identification and further characterization of gp180 and its exploitation for immunomodulatory purposes that the present invention is directed.